Effects of chitinase-3-like protein 1 on brain death-induced hepatocyte apoptosis via PAR2-JNK-caspase-3

  • Biochem Biophys Res Commun. 2021 May 7;552:150-156. doi: 10.1016/j.bbrc.2021.03.048.
Ze-Xin Li  1 ,  Dong-Jing Yang  2 ,  Zhong-Kun Huo  2 ,  Pei-Hao Wen  3 ,  Bo-Wen Hu  3 ,  Zhi-Hui Wang  3 ,  Wen-Zhi Guo  2 ,  Shui-Jun Zhang  4
Affiliations
  • 1. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Medical Engineering and Technology Center of Organ Transplantation, Zhengzhou, Henan, China; Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation, Zhengzhou, Henan, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China.
  • 2. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Medical Engineering and Technology Center of Organ Transplantation, Zhengzhou, Henan, China; Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation, Zhengzhou, Henan, China.
  • 3. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Medical Engineering and Technology Center of Organ Transplantation, Zhengzhou, Henan, China.
  • 4. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Medical Engineering and Technology Center of Organ Transplantation, Zhengzhou, Henan, China; Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation, Zhengzhou, Henan, China. Electronic address: [email protected].
PMID: 33744763 DOI: 10.1016/j.bbrc.2021.03.048
Abstract

Hepatocyte Apoptosis is a crucial factor affecting liver quality in brain-dead donors. The identification of key molecular proteins involved in brain-death (BD)-induced hepatocyte Apoptosis may help determine an effective method for improving the quality of livers from brain-dead donors. In this study, we used in vivo and in vitro models to investigate the role of chitinase-3-like protein 1 (CHI3L1) in promoting liver cell Apoptosis after BD. Chitin was used to inhibit CHI3L1 in a rat model of BD. Macrophage polarization of THP-1 cells and hypoxia/reoxygenation (H/R) of LO-2 cells were used to mimic BD-induced cell stress in liver. We found that CHI3L1 played a vital role in promoting liver cell Apoptosis. Six hours after BD, CHI3L1 expression was significantly upregulated in liver macrophages and was associated with BD-induced M1 polarization of these cells. In liver cells cultured under H/R conditions, recombinant CHI3L1 activated the Protease-activated Receptor 2 (PAR2)/c-June N-terminal kinase (JNK) apoptotic pathway and aggravated Apoptosis. Compared with the control group, chitin particles inhibited the expression of CHI3L1 in the liver of brain dead rats, thereby reducing activation of the hepatocyte surface receptor, PAR2, and its downstream JNK/Caspase-3 signaling pathway, ultimately reducing hepatocyte Apoptosis. In conclusion, our results indicate that CHI3L1 relies on a PAR2/JNK-mediated mechanism to promote BD-induced hepatocyte Apoptosis.

Keywords
Apoptosis; Brain death; Chitinase-3-like protein 1; Hepatocyte.
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